Monday, August 2, 2021

New Study Uncovers Details Behind the Body’s Response to Stress

The biological mechanisms behind stress-related psychiatric conditions, including major depressive disorder and post-traumatic stress disorder (PTSD), are poorly understood.

The findings of this study on stress will open new directions for future research.
‘The findings of this study will open new directions for future research.’ (Image: via pixabay / CC0 1.0)

New research now details the interplay between proteins involved in controlling the body’s stress response and points to potential therapeutic targets when this response goes awry. The study, which was conducted by an international team led by investigators at McLean Hospital, appears in the journal Cell Reports.

Stress study highlights

  • New research reveals how key proteins interact to regulate the body’s response to stress
  • Targeting these proteins may help treat or prevent stress-related psychiatric disorders

Lead author Jakob Hartmann, Ph.D. is an assistant neuroscientist in the Neurobiology of Fear Laboratory at McLean and an instructor in psychiatry at Harvard Medical School. Hartmann said:

“A dysregulated stress response of the body can be damaging for the brain and promote susceptibility to mood and anxiety disorders. A key brain region involved in the regulation of the stress response is the hippocampus. The idea for this study occurred to us when we noticed interesting distinctions in hippocampal localization of three important stress-regulating proteins.”

The researchers’ experiments in non-human tissue and postmortem brain tissue revealed how these proteins—the glucocorticoid receptor (GR), the mineralocorticoid receptor (MR), and the FK506-binding protein 51 (FKBP5)—interact with each other. Specifically, MRs, rather than GRs, control the production of FKBP5 under normal conditions. FKBP5 decreases GRs’ sensitivity to binding stress hormones during stressful situations.

‘Our data further underline the important but largely unappreciated role of MR signaling in stress-related psychiatric disorders.’ (Image: via pixabay / CC0 1.0)

FKBP5 appears to fine-tune the stress response by acting as a mediator of the MR:GR balance in the hippocampus. Senior author Kerry J. Ressler, MD, Ph.D., who is the chief scientific officer at McLean Hospital, chief of McLean’s Division of Depression and Anxiety Disorders, and a professor in psychiatry at Harvard Medical School, said:

“Our findings suggest that therapeutic targeting of GR, MR, and FKBP5 may be complementary in manipulating central and peripheral regulation of stress. Moreover, our data further underline the important but largely unappreciated role of MR signaling in stress-related psychiatric disorders. The findings of this study will open new directions for future research.”

Provided by: McLean Hospital [Note: Materials may be edited for content and length.]

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Troy Oakes
Troy was born and raised in Australia and has always wanted to know why and how things work, which led him to his love for science. He is a professional photographer and enjoys taking pictures of Australia's beautiful landscapes. He is also a professional storm chaser where he currently lives in Hervey Bay, Australia.
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